The overall objective of this research is the elucidation of the molecular mechanisms involved in the induction of tumors by chemicals. This objective is being approached through the characterization of the proximate and ultimate carcinogenic metabolites of administered carcinogens and by an analysis of the reactions of the ultimate carcinogenic metabolites with tissue constituents, especially nucleic acids and proteins. The basic concepts in these studies are that the ultimate carcinogenic derivatives of the known chemical carcinogens are strong electrophilic reactants and that the induction of the neoplastic process requires some type of interaction between the ultimate carcinogenic derivatives and informational cellular macromolecules. The carcinogens being studied, both in vivo and in vitro, include 2- acetylaminofluorene and related carcinogenic amides, safrole and related benzylic and allylic derivatives, aflatoxin B1 and the diphenyl acetylenic carbamates.